Activation of hypoxia-inducible factor 1 attenuates periapical inflammation and bone loss.
Activation of hypoxia-inducible factor 1 attenuates periapical inflammation and bone loss.
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低氧诱导因子-1的激活可减轻根尖周炎和骨丢失。
DOI：
10.1038/s41368-018-0015-0
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发表时间：
2018-04-13
影响因子：
14.9
通讯作者：
Sasaki H
中科院分区：
文献类型：
--
作者：
Hirai K;Furusho H;Hirota K;Sasaki H
缺氧（低氧水平）是感染期间的一个重要特征，并影响宿主的防御机制。宿主已经进化出针对缺氧的特异性反应，其强烈依赖于缺氧诱导因子1（HIF-1）的激活。缺氧干扰HIF-1 α亚基（HIF-1α）的降解，导致HIF-1α稳定，与HIF-1 β亚基（HIF-1β）异源二聚化，随后激活HIF-1通路。根尖牙周炎（根尖周病变）是牙髓感染的结果，最终导致牙齿支持组织（包括牙槽骨）的破坏。到目前为止，HIF-1在根尖周病变中的作用尚未得到系统的研究。在本研究中，我们使用两种HIF-1α激活策略，即二甲基草酰甘氨酸（DMOG）和腺病毒诱导的组成型活性HIF-1α（CA-HIF 1A），确定HIF-1在特征明确的小鼠根尖周病变模型中的作用。DMOG和CA-HIF 1A均减轻根尖周炎症和组织破坏。在体内的衰减与核因子-κ B（NF-κB）和骨钙素基因表达的下调有关。这两种药物还抑制NF-κB活化和随后巨噬细胞产生促炎细胞因子。此外，DMOG激活HIF-1α特异性抑制脂多糖刺激的巨噬细胞分化为M1细胞，增加M2巨噬细胞对M1细胞的比例。总之，我们的数据表明，HIF-1的活化通过下调NF-κB、促炎细胞因子、M1巨噬细胞和破骨细胞生成在根尖牙周炎的发展中起保护作用。靶向参与身体对低内部氧浓度反应的蛋白质复合物可以帮助治疗破坏性牙根炎症。来自密歇根大学的Hajime Sasaki及其在美国和日本的同事研究了蛋白质复合物HIF-1在口腔炎症中的作用。它们在小鼠磨牙的根部区域引起病变，使其暴露于口腔细菌，从而导致炎症。他们给小鼠注射了两种激活HIF-1通路的药物之一。病变中的炎症和骨破坏均减少。HIF-1通路的激活关闭了另一条称为NF-κB的通路，该通路参与了对感染的免疫反应。它还关闭了与骨骼破坏有关的基因。结果表明，HIF-1对牙根病变具有保护作用，并可能在其治疗中发挥作用，有待进一步研究。
Hypoxia (low oxygen level) is an important feature during infections and affects the host defence mechanisms. The host has evolved specific responses to address hypoxia, which are strongly dependent on the activation of hypoxia-inducible factor 1 (HIF-1). Hypoxia interferes degradation of HIF-1 alpha subunit (HIF-1α), leading to stabilisation of HIF-1α, heterodimerization with HIF-1 beta subunit (HIF-1β) and subsequent activation of HIF-1 pathway. Apical periodontitis (periapical lesion) is a consequence of endodontic infection and ultimately results in destruction of tooth-supporting tissue, including alveolar bone. Thus far, the role of HIF-1 in periapical lesions has not been systematically examined. In the present study, we determined the role of HIF-1 in a well-characterised mouse periapical lesion model using two HIF-1α-activating strategies, dimethyloxalylglycine (DMOG) and adenovirus-induced constitutively active HIF-1α (CA-HIF1A). Both DMOG and CA-HIF1A attenuated periapical inflammation and tissue destruction. The attenuation in vivo was associated with downregulation of nuclear factor-κappa B (NF-κB) and osteoclastic gene expressions. These two agents also suppressed NF-κB activation and subsequent production of proinflammatory cytokines by macrophages. Furthermore, activation of HIF-1α by DMOG specifically suppressed lipopolysaccharide-stimulated macrophage differentiation into M1 cells, increasing the ratio of M2 macrophages against M1 cells. Taken together, our data indicated that activation of HIF-1 plays a protective role in the development of apical periodontitis via downregulation of NF-κB, proinflammatory cytokines, M1 macrophages and osteoclastogenesis. Targeting a protein complex involved in the body’s response to low internal oxygen concentrations could help treat destructive tooth root inflammations. Hajime Sasaki from the University of Michigan and colleagues in the U.S. and Japan investigated the role of the protein complex HIF-1 in oral inflammation. They induced lesions in the root area of molar teeth in mice, exposing them to oral bacteria, which led to inflammation. They injected the mice with one of two agents that activate the HIF-1 pathway. Inflammation and bone destruction in the lesions were both reduced. Activation of the HIF-1 pathway turned off another pathway, called NF-κB, involved in the immune response to infection. It also turned off genes involved in bone destruction. The results indicate that HIF-1 has a protective effect on tooth root lesions and could play a role in their treatment pending further investigations.
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影响因子：
29.4
作者：
Cummins, Eoin P.;Seeballuck, Fergal;Taylor, Cormac T.
通讯作者：
Taylor, Cormac T.
羟化酶抑制剂二甲氧亚甘氨酸通过巨噬细胞的替代激活和B1细胞产生的IL-10产生来减轻内毒性休克。
DOI：
10.1097/shk.0b013e318225ad7e
发表时间：
2011-09
期刊：
Shock (Augusta, Ga.)
影响因子：
--
作者：
Hams E;Saunders SP;Cummins EP;O'Connor A;Tambuwala MT;Gallagher WM;Byrne A;Campos-Torres A;Moynagh PM;Jobin C;Taylor CT;Fallon PG
通讯作者：
Fallon PG
影响因子：
9.4
作者：
KOKEGUCHI, S;KATO, K;MURAYAMA, Y
通讯作者：
MURAYAMA, Y
缺氧诱导的信号蛋白 7A 的表达与实验诱导的根尖周病变中炎症和破骨细胞生成的严重程度相关。
影响因子：
3
作者：
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通讯作者：
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影响因子：
4.2
作者：
Martinez, Zulema Rosalia Arias;Naruishi, Koji;Takashiba, Shogo
通讯作者：
Takashiba, Shogo